Tag: pericytes

The laboratory of Marni D. Boppart at the Beckman Inst. for Advanced Science and Technology in Urbana, Illinois has published a very interesting study that shows that injections of mesenchymal stem cells (MSCs) into mice after they have exercised increases the number of new blood vessels formed in skeletal muscle.

Early last year, Boppart’s laboratory showed that exercise in mice induces a population of mesenchymal stem cells located near blood vessels (pericytes) to migrate into muscles and form new muscle fibers. A particular adhesion molecule known as integrin α7 is responsible for the movement of MSCs into the muscle. Boppart and his colleagues showed that engineering mice that made extra α7 integrin had muscles that were filled with more stem cells making new muscle than their normal litter mates after exercise.

More recently, Boppart and his colleagues have injected cultured MSCs into the muscles of mice after the mice had exercised by running downhill. The mice injected with MSCs had more blood vessels in their muscles than mice than received no such injections. The blood vessels in the MSC-injected mice were also larger. Further work showed that the MSCs produced a veritable smorgasbord of angiogenic factors, which are molecules that induce the formation of blood vessels.

Thus MSCs, in response to exercise, can increase muscle mass as a result of exercise and increase the density and diameter of blood vessels.

Dr. Centeno at the Regenexx blog site wonders if stem-cell doping will be the next trick athletes will use to increase their muscle size and strength. Such a trick would be completely undetectable with contemporary technology, and it seems as though this might be a genuine possibility.

The ability of endothelial progenitor cells or EPCs to repair skeletal muscle is well established, but the ability of these cells to repair a damaged heart is unknown. Johnny Huard from the McGowan Institute for Regenerative Medicine at the University of Pittsburgh and his group investigated the therapeutic capabilities of human blood vessel-derived EPCs that had been isolated from skeletal muscle to treat heart disease in mice.

When mice that had been given infusions of EPCs after a heart attack were compared with mice that had received a placebo, the EPC transplanted mice definitely fared much better. Echocardiographic studies of the hearts showed that EPC transplantation reduced enlargement of the left ventricle (the main pumping chamber of the heart), and also significantly improved the ability of the heart to contract.

In addition to comparing the ability of EPCs to improve the function of the heart after a heart attack with placebos, they were also compared to stem cells known to make skeletal muscle. These stem cells are called “CD56+ myogenic progenitor cells,” which is a mouthful. CD56+ myogenic progenitor cells or CD56+ MPCs can form skeletal muscle; and infusions of them can improve the structure of the heart after a heart attack and prevent it from deteriorating. However, transplanted EPCs were superior to CD56+ MPCs in their ability to heal the heart after a heart attack.

The transplanted EPCs were able to substantially reduced scarring in the heart, and significantly reduced inflammation in the heart. In fact, then the culture medium in which EPCs were grown was injected into mouse hearts after a heart attack, this medium also suppressed inflammation in the heart.

When Huard and his co-workers examined the genes made in the EPCs, they found that these stem cells cranked out proteins known to decrease inflammation (IL-6, LIF, COX-2 and HMOX-1 for those who are interested), especially when the cells were grown under low oxygen conditions. This is significant because in the heart after a heart attack, blood vessels have died off and the supply of blood to the heart is compromised. The fact that these cells are able to do this under these harsh conditions shows that they make exactly the most desirable molecules under these conditions.

The biggest boon for these cells came from examinations of blood vessel formation in the heart. Blood vessel production in the EPC-transplanted hearts was significantly increased. The EPCs formed a host of new blood vessels and extending “microvascular structures” or smaller supporting blood vessels and larger capillary networks too.

Once again, when grown under oxygen poor conditions, the EPCs jacked up their expression of pro-blood vessel-making molecules (VEGF-A, PDGF-β, TGF-β1 and their receptors). When EPCs were labeled with a green-glowing protein, fluorescence tracking showed that they actually fused with heart cells, although it must be emphasized that this was a minor event.

These pre-clinical studies show remarkable improvements in the heart after a heart attack, and they apparently induce these improvements through several different mechanisms. They make new structures and they secrete useful molecules. These significantly successful results should provide the basis for clinical trials with these cells.